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Summary
Several pharmaceutical compounds were evaluated for their ability to selectively inhibit activated coagulation factor-XIII-like enzyme activity (eg, Xllla*) in pooled equine plasma. Presence of coagulation factor-XIIIa*-like enzyme activity in plasma was established by assay procedures involving incorporation of the fluorescent amine compound, monodansylcadaverine, into purified casein, which served as a protein substrate.
Pharmaceuticals inhibitory to coagulation factor-XIIIa*-like enzyme activity were recognized by plasma gel formation of high spectrophotometric transmittance (transparency), solubility of transparent fibrin gels in concentrated urea solution, in conjunction with simultaneous depletion of native fibrinogen fractions, and production of fibrin monomer. Compounds acting primarily as anticoagulants were recognized by lack of plasma gel formation, but retaining high spectrophotometric transmittance and no detectable depletion of native fibrinogen fractions. Compounds failing to inhibit either thrombin-mediated fibrinogen-fibrin transformation (ie, coagulation) or coagulation factor-XIIIa*-like enzyme activity were recognized by opaque plasma gels caused by fibrin polymerization, low spectrophotometric transmittance values, and coinciding with depletion of native fibrinogen fractions.
Pharmaceuticals capable of exerting selective inhibition of coagulation factor-XIIIa*-like enzyme activity were further classified as competitive inhibitors of phase 1 (carbamide) or phase 2 (terminal amine) of the transglutamination process.
Summary
The ability of polysulfated glycosaminoglycans (psgag) to inhibit the complement cascade was evaluated. The role of complement in inflammation and infection has been well documented. Inhibition of the complement cascade by psgag could explain why intra-articularly administered psgag diminish diarthrodial joint inflammation and potentiate septic arthritis in horses.
Hemolytic complement testing was performed to evaluate the effect of psgag on the equine classical and alternate pathways of complement, using rabbit erythrocytes as the target cells. Concentration of psgag between 0.2 mg/ml and 0.6 mg/ml significantly (P< 0.05) inhibited equine complement in dose-related fashion. Further increase in complement inhibition was not observed at psgag concentration >0.6 mg/ml. Difference was not apparent in the extent of inhibition of complement from each of the 4 horses tested. Polysulfated glycosaminoglycans appeared to inhibit the classical and alternate complement pathways equally, indicating possible effect on complement components common to both pathways. Heat inactivation of complement function completely inhibited (P<0.01) the hemolytic activity of the serum from all horses.
SUMMARY
Furosemide, which commonly is used as a prophylactic treatment for exercise-induced pulmonary hemorrhage in horses, may mediate hemodynamic changes during exercise by altering prostaglandin metabolism. To determine if furosemide's hemodynamic effects during exercise in horses could be reversed, cyclooxygenase inhibitors were administered with furosemide. Four treatments were administered 4 hours prior to treadmill exercise at 9 and 13 m/s. They included a control treatment (10 ml of 0.9% NaCl solution, iv), furosemide (1 mg/kg of body weight, iv) administered alone, and furosemide in combination with phenylbutazone (4 mg/kg, iv, q 12 h for 2 days) or with flunixin meglumine (1.1 mg/kg, iv, on the day of experiment). Five horses were randomly assigned to complete all treatments. Physiologic variables at rest prior to exercise were not influenced by treatments. Furosemide, administered alone, reduced mean right atrial pressure and mean pulmonary artery pressure during exercise. The combinations of furosemide and flunixin meglumine or furosemide and phenylbutazone, at both levels of exercise intensity, returned mean right atrial pressure and mean pulmonary artery pressure to the value of the control treatment. During rest and exercise, plasma lactate concentration, pcv, heart rate, mean carotid artery pressure, oxygen consumption, carbon dioxide elimination, and cardiac output were not altered by any of the treatments. At 5 minutes after exercise, the administration of furosemide, alone or with phenylbutazone, reduced mean right atrial pressure. Other measured variables were not significantly influenced by treatments during recovery from exercise. These results suggested that cyclooxygenase inhibition partially reverses the decrease in mean right atrial pressure or pulmonary artery pressure induced by furosemide during exercise. Furosemide may mediate some of its physiologic activities in exercising horses through the cyclooxygenase pathway.
Summary
Four hours prior to exercise on a high-speed treadmill, 4 dosages of furosemide (0.25, 0.50, 1.0, and 2.0 mg/kg of body weight) and a control treatment (10 ml of 0.9% NaCl) were administered iv to 6 horses. Carotid arterial pressure (cap), pulmonary arterial pressure (pap), and heart rate were not different in resting horses before and 4 hours after furosemide administration. Furosemide at dosage of 2 mg/kg reduced resting right atrial pressure (rap) 4 hours after furosemide injection. During exercise, increases in treadmill speed were associated with increases in rap, cap, pap, and heart rate. Furosemide (0.25 to 2 mg/kg), administered 4 hours before exercise, reduced rap and pap during exercise in dose-dependent manner, but did not influence heart rate. Mean cap was reduced by the 2-mg/kg furosemide dosage during exercise at 9 and 11 m/s, but not at 13 m/s. During recovery, only rap was decreased by furosemide administration. Plasma lactate concentration was not significantly influenced by furosemide administration. Furosemide did not influence pcv or hemoglobin concentration at rest prior to exercise, but did increase both variables in dose-dependent manner during exercise and recovery. However, the magnitude of the changes in pcv and hemoglobin concentration were small in comparison with changes in rap and pap, and indicate that furosemide has other properties in addition to its diuretic activities. Furosemide may mediate some of its cardiopulmonary effects by vasodilatory activities that directly lower pulmonary arterial pressure, but also increase venous capacitance, thereby reducing venous return to the atria and cardiac filling.
Abstract
OBJECTIVE
To investigate the effects and duration of orally administered prednisolone on renal function evaluated by glomerular filtration rate (GFR) determination and creatinine (Cr) and symmetric dimethylarginine (SDMA) concentrations as well as on urinalysis, electrolytes, and hydric status in healthy dogs.
ANIMALS
14 healthy Beagles.
PROCEDURES
In this prospective double-masked placebo-controlled study, dogs were randomized after baseline evaluation to receive a 7-day course of either prednisolone (1.5 to 2.0 mg/kg, PO, q 12 h) or a placebo. A repeated-measure design was performed, each dog participating in 4 successive sampling sessions. Clinical data, systolic blood pressure, CBC, and biochemical analyses including serum SDMA concentration, GFR determination, urine output quantification, and complete urinalysis were performed for all dogs the day before (D0) and at the end of steroid administration (D7) as well as 2 weeks (D21) and 4 weeks (D35) after the end of treatment.
RESULTS
At D7, when compared with baseline, GFR increased significantly in treated dogs, whereas creatinine and SDMA concentrations decreased significantly. GFR and Cr but not SDMA modifications persisted significantly at D21. None of the variables differed significantly from baseline at D35. The OR of presenting an albumin band on urine electrophoresis was 2.4 times as high in treated versus control dogs (OR, 36; 95% CI, 1.8 to 719.4; P = 0.02).
CLINICAL RELEVANCE
A short-term course of immune-suppressive prednisolone treatment in healthy dogs leads to a sustained but reversible renal hyperfiltration state. Modification in electrolytic variables can affect the clinical interpretation of blood work in such patients.
